Authors: Rau, S.¹; Autschbach, F.¹; Riedel, H. D.¹; Konig, J.²; Kulaksiz, H.¹; Stiehl, A.¹; Riemann, J. F.³; Rost, D.

Source: European Journal of Clinical Investigation, Volume 38, Number 2, February 2008 , pp. 134-142(9)

Publisher: Wiley-Blackwell

Abstract:

Background 

Cholangiocellular carcinomas and gallbladder carcinomas are highly aggressive tumours with a poor prognosis and are generally regarded as chemoresistant tumours. Overexpression of ATP-binding cassette transporters of the multidrug resistance protein (MDR) and multidrug resistance-related protein (MRP) family in cancer cells is a major cause for the multidrug resistance phenotype in vitro and in vivo. To further define the role of MRP family members in biliary tract cancer, we studied the expression and localization of MRP2 and MRP3 in cholangiocellular carcinomas and gallbladder carcinomas. Materials and methods 

The expression and cellular localization of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas and gallbladder carcinomas were analysed by immunohistochemistry using isoform-specific antibodies. Expression of MRP isoforms was studied in vitro in Mz-ChA-1 cells derived from gallbladder adenocarcinoma by reverse transcription-polymerase chain reaction (RT-PCR), immunoblotting and immunofluorescence microscopy. Results 

Mz-ChA-1 cells constitutively expressed MDR P-glycoproteins, MRP1, MRP2 and MRP3 by RT-PCR, immunoblotting and immunofluorescence microscopy. MRP2 and MRP3 are expressed in the respective apical and basolateral membrane domains. MRP3 was the predominant MRP isoform in gallbladder carcinomas (93%) and cholangiocellular carcinomas (57%), whereas MRP2 expression was detected in only 29% of gallbladder carcinomas and was undetectable in cholangiocellular carcinomas. Conclusions 

Our findings suggest that the intrinsic multidrug resistance of cholangiocellular and gallbladder carcinomas seems to be independent of MRP2 expression while the expression of MRP3 may contribute to the MDR phenotype.

Eur J Clin Invest 2008; 38 (2): 134-142

Keywords: Chemotherapy; cholangiocellular carcinoma; gallbladder carcinoma; multidrug resistance; Mz-ChA-1

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2362.2007.01916.x

Affiliations: 1: University of Heidelberg, Heidelberg, Germany, 2: Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany, 3: Klinikum der Stadt Ludwighafen, Ludwigshafen, Germany

Publication date: 2008-02-01

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